Projet ANR MIGAD

Type 2 Diabetes (T2D) is the main epidemic of this century. A recent hypothesis of medical research is that an important cause of T2D may be the abnormal regulation of glucose absorption in the small intestine. The objective of the present project is to investigate the relative contribution of each regulatory  mechanism in the postprandial glucose response, with a particular focus on the mechanism of intestinal glucose absorption. Indeed, despite of many experimental observations, this question remains poorly investigated. Both whole­body physiolog­ical and cellular level will be considered. We will adopt a systems biology approach based on formal computational models enhanced by wet­lab experiments. Unlike all the models already available and defined by means of differen­tial equations, we will propose to work with reaction networks. Those are metamodels that add a graph structure to ordinary differential equations (ODEs) and allow for a wider range of analysis methods from computational systems biology. We will also study novel analysis methods for reaction networks able to deal with aspects of postprandial glucose response and diabetes. The hope is to improve the identification of the causes of T2D and, in the longer run, the prediction of appropriate therapies based on reaction networks.

• Partner 1: BioComputing research group at CRIStAL lab, UMR CNRS 9189 (Univ. Lille, CNRS, Centrale Institut)
• Partnet 2: Translational Research Laboratory for Diabetes, UMR 1190 (Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille)
• Partner 3: Récepteurs nucléaires, maladies métaboliques et cardiovasculaires, UMR 1011 (Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille)

WP 1: Modeling postprandial glucose response

• Task 1: In vivo experiments
• Task 2: Assessment of Dalla Man’s model to predict and explain PGR
• Task 3: Design of reliable and explainable reaction networks for PGR

WP 2: Analysing Homeostatic Reaction Networks and Glucose Dynamics

• Task 1: Study integral feedback control in reaction networks.
• Task 2: Computing the size of the response signal for homeostatic reaction networks.
• Task 3: Abstract interpretation for approximating signal differences of reaction networks.

WP 3: Modeling IGA at the cellular level

• Task 1: Experiments.
• Task 2: On the relative contribution of SGLT1 and GLUT2 to IGA.
• Task 3: Modeling and analysis of sub­cellular SGLT1 and GLUT2 trafficking.

• Danilo Dursoniah, Maxime Folschette, Rebecca Goutchtat, Violeta Raverdy, François Pattou, Cédric Lhoussaine
  Modeling Intestinal Glucose Absorption from D-xylose Data (Best Paper Award)
  15th International Conference on Bioinformatics, Models, Methods and Algorithms, Feb 2024, Rome, Italy

• Joachim Niehren, Cédric Lhoussaine, Athénaïs Vaginay
  Core SBML and its Formal Semantics
  CMSB 2023 - 21th Int. Conference on Computational Methods in Systems Biology, Sep 2023, Luxembourg, Luxembourg

• Danilo Dursoniah, Maxime Folschette, Cédric Lhoussaine, Rebecca Goutchtat, François Pattou, Violeta Raverdy
  Limits of a Glucose-Insulin Model to Investigate Intestinal Absorption in Type 2 Diabetes
  BIOTECHNO 2021 : 13th Int. Conference on Bioinformatics, Biocomputational Systems and Biotechnologies, May 2021, Valencia, Spain. pp.4-7